DRUG NAME: Ofatumumab

Transcription

1 DRUG NAME: Ofatumumab SYNONYM(S): GSK , 1 HuMax-CD20 1 COMMON TRADE NAME(S): ARZERRA CLASSIFICATION: monoclonal antibody Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: Ofatumumab is a fully human immunoglobulin (G1 kappa) monoclonal antibody which targets the CD20 molecule on human B-cells. Binding of ofatumumab causes clustering of CD20 on the cell surface and cell death through the induction of complement-mediated and antibody dependent cell-mediated cytotoxicity. 1 USES: Primary uses: Other uses: Leukemia, chronic lymphocytic 2,3 Lymphoma, follicular 2 *Health Canada approved indication Lymphoma, diffuse large B-cell 2 Waldenstrom s macroglobulinemia 1 SPECIAL PRECAUTIONS: fulminant and fatal hepatitis B virus infection and reactivation can occur; screen those at risk and monitor for signs of active infection 4 premedicate with analgesics, antihistamines, and corticosteroids before each infusion to prevent hypersensitivity reactions 4 response to vaccination may be impaired when B cells are depleted; safety of live viral vaccines during or following ofatumumab treatment is unknown 2,4 statins were found to reduce the in vitro ability of ofatumumab to induce cell lysis 1 SIDE EFFECTS: The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials. When placebo-controlled trials are available, adverse events are included if the incidence is >5% higher in the treatment group. ORGAN SITE SIDE EFFECT Clinically important side effects are in bold, italics blood and lymphatic system/ febrile neutropenia cardiac anemia (16-17%, severe 5-8%) neutropenia (15-42%) 3,4 ; may be prolonged ( 1 week) 4 thrombocytopenia, may be prolonged ( 1 week) hypertension (5-8%) hypotension (3-5%) tachycardia (5-7%, severe 2%) BC Cancer Agency Cancer Drug Manual Page 1 of 5 Ofatumumab (interim monograph)

2 ORGAN SITE SIDE EFFECT gastrointestinal general disorders and administration site conditions infections and infestations musculoskeletal and connective tissue Clinically important side effects are in bold, italics emetogenic potential: rare 5 diarrhea (16-19%) 3,4 intestinal obstruction nausea (11-12%) extravasation hazard: none 6 chills (8-10%) edema, peripheral (8-9%, severe 2%) fatigue (15%) infusion reactions (38-44% with first infusion; 29% with second infusion; 7% at 12 th infusion) 3,4 ; see paragraph following Side Effects table pyrexia (15-25%, severe 3-5%) 3,4 bronchitis (11-19%, severe 2%) Herpes zoster (6-7%, severe 1-2%) Hepatitis B virus infection or reactivation nasopharyngitis (8%) pneumonia (23-25%, severe 14-15%) sepsis (8-10%, severe 8-10%) sinusitis (3-5%, severe 2%) upper respiratory tract infections (3-11%) back pain (8-12%, 1-2%) muscle spasms (3-5%) nervous system headache (6-7%) psychiatric insomnia (7-10%) respiratory, thoracic and cough (18-19%) 3,4 mediastinal dyspnea (13-19%; severe 2-5%) 3,4 skin and subcutaneous tissue hyperhidrosis (5%) rash (10-17%, severe 2%) 3,4 urticaria (5-8%) Adapted from standard reference 4 unless specified otherwise. Infectious events are reported by 70% of patients and may be bacterial, viral, or fungal 4 Infections are usually grade 1 or 2 in severity, but major infections are reported in 23-32% and are sometimes fatal. 3,4 Among grade 3 or 4 infections, pneumonia and other respiratory tract infections are the most common. 3 Infusion reactions may manifest as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema. Reactions occur more frequently with the first two infusions, and tend to decrease with subsequent infusions. Premedication before each infusion with analgesics, antihistamines, and glucocorticoids is recommended. Infusion reactions require immediate interruption of the infusion and symptomatic treatment if necessary. Infusions BC Cancer Agency Cancer Drug Manual Page 2 of 5 Ofatumumab (interim monograph)

3 should not be resumed for grade 4 or greater reactions. 2,4 Patients with a history of decreased pulmonary function are at greater risk of pulmonary complications from severe reactions. 1,2 Monitor liver function tests: ofatumumab should be discontinued if ALT >3xULN and direct bilirubin >2xULN; ALT >8xULN; or ALT remains >5xULN for 2 weeks Patients with ALT >3xULN but 5xULN and bilirubin 2xULN, without symptoms of hepatitis or rash, should be monitored until liver chemistries return to baseline or stabilize. 2 Progressive multifocal leukoencephalopathy (PML), sometimes fatal, can occur with ofatumumab. Monitor for new onset, or changes in, pre-existing neurological symptoms (i.e., confusion, dizziness, loss of balance, difficulty walking or talking, or vision problems), and discontinue ofatumumab if PML is suspected. 4 SUPPLY AND STORAGE: Injection: GlaxoSmithKline supplies ofatumumab as a preservative-free liquid concentrate in 100mg/5 ml and 1000 mg/50 ml single use vials. Refrigerate. Do NOT freeze. Protect from light. 4 For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix. SOLUTION PREPARATION AND COMPATIBILITY: For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix. Additional information: all doses are to be prepared in sodium chloride injection 0.9% 1000 ml (doses of 300 mg must be prepared in 1 x 1000 ml bag; doses of 2000 mg may be prepared in either 1 x 1000 ml bag or 2 x 500 ml bags) 2 flush lines with sodium chloride injection 0.9% before and after each dose 2 infusions should be started within 12 hours of preparation 4 administer with an in-line filter set 2 do NOT shake 2 may contain a small amount of visible, translucent or white particles; do not use if solution is discolored or cloudy or if foreign particulate matter is present 2 Compatibility: consult detailed reference PARENTERAL ADMINISTRATION: BCCA administration guideline noted in bold, italics Subcutaneous has been used 1 Intramuscular Direct intravenous do NOT use 4 BC Cancer Agency Cancer Drug Manual Page 3 of 5 Ofatumumab (interim monograph)

4 Intermittent infusion 2 BCCA administration guideline noted in bold, italics dose 1: 300 mg in 1000 ml initiate infusion at 12 ml/h If no infusion reaction occurs during the first 30 minutes, infusion rate should be increased every 30 minutes to a maximum rate of 400 ml/h as shown in the following table. Infusion rate of 1st Ofatumumab infusion Time ml/hour 0-30 minutes minutes minutes minutes minutes minutes minutes 400 If an infusion reaction develops, the infusion should be temporarily interrupted. Infusion rate should be restarted at half the rate at the time the infusion was paused (but not less than 12 ml/h) and increased according to the table, based on patient tolerance and prescriber discretion. doses 2-12: 2000 mg in 1000 ml if the previous infusion was completed without grade 3 infusion-associated reactions, subsequent infusions can start at 25 ml/h; infusion rate should be doubled every 30 minutes to a maximum rate of 400 ml/h as shown in the following table. Infusion rate of subsequent Ofatumumab infusions Time ml/hour 0 30 minutes minutes minutes minutes minutes 400 Continuous infusion Intraperitoneal Intrapleural Intrathecal Intra-arterial Intravesical If the previous infusion was completed with grade 3 infusion-associated reactions, the subsequent infusion should start at a rate of 12 ml/h; infusion rate should be doubled every 30 minutes to a maximum rate of 400 ml/h. BC Cancer Agency Cancer Drug Manual Page 4 of 5 Ofatumumab (interim monograph)

5 DOSAGE GUIDELINES: Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count (ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to cytotoxic/radiation therapy or with other toxicities. Adults: BCCA usual dose noted in bold, italics Cycle Length: Intravenous: 2 n/a: For a total of 12 doses over 24 weeks: dose 1: 300 mg IV for one dose on day 1; doses 2-8: 2000 mg IV for one dose weekly for 7 weeks; and then, starting 4 weeks later, doses 9-12: 2000 mg IV for one dose every 4 weeks (total dose per cycle 22,300 mg) Premedication regimen: 2 To be given within 30 minutes to 2 hours prior to each ofatumumab infusion, as shown in the following table, to minimize infusion reactions: Pre-medication Requirements prior to Ofatumumab Infusions 2 Dose/Infusion # Acetaminophen (po) or equivalent Antihistamine (iv or po) diphenhydramine or equivalent Glucocorticoid (iv) prednisolone or equivalent 1st 1000 mg 50 mg 50 mg 2nd 1000 mg 50 mg 50 mg 3rd and subsequent 1000 mg 50 mg 0 50 mg* * If the 2nd infusion has been completed without the patient experiencing any AE > Grade 3, premedication with glucocorticoid may be reduced or omitted before the 3rd and subsequent infusions at the discretion of the investigator. 2 It has been recommended in some sources that corticosteroid doses should be given unreduced for dose 9 as well as for doses 1 and 2. 4,7 REFERENCES: 1. GlaxoSmithKline. Ofatumumab (GSK ) Investigator's Brochure (version 4). Uxbridge, United Kingdom; 17 March GlaxoSmithKline. Guidance Booklet: compassionate use access of ofatumumab for patients with chronic lymphocytic leukemia (CLL) who are refractory to fludarabine and alemtuzumab or who are deemed inappropriate for alemtuzumab therapy. version 5; 1 February Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2010;28(10): GlaxoSmithKline. ARZERRA Full Prescribing Information. Research Triangle Park, North Carolina; September, BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Adults. Vancouver, British Columbia: BC Cancer Agency; 1 Mar BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and Management of Extravasation of Chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 February Glaxo Group Ltd. ARZERRA summary of product characteristics. Middlesex, United Kingdom; 21 April BC Cancer Agency Cancer Drug Manual Page 5 of 5 Ofatumumab (interim monograph)